The PI has directed the Weill Medical College Bio Mass Spectrometry Core Facility since its inception, on November 1, 1997. This facility was created to service the biological mass spectrometry needs of NIH- supported investigators at Weill Medical College and neighboring institutions (New York Presbyterian Hospital and The Hospital for Special Surgery) and owes to a previously awarded NRCC shared instrument grant. The facility has been continuously active, staffed by 1.5 FTEs, and provides the sole source of macromolecule mass spectrometric analyses to its user-base. Nonetheless, a key instrument is critically outdated in its functionality. This proposal seeks funds to purchase a state-of-the-art matrix-assisted laser desorption ionization- time-of flight (MALDI-TOF), needed by a large group of NIH-supported investigators, 12 major users are specified herein. The MALDI-TOF mass spectrometer will be used mainly for accurate and sensitive mass analysis of proteins, peptides and derivatives bearing chemical modifications. Additionally, the instrument will be used for analysis of protein complexes and definitive identification of unknown proteins on 1D and 2D gels. We have selected a MALDI-TOF mass spectrometer and data analysis system that optimally meets our combined needs. Advantages of the selected instrument are: (a) ability to analyze complex protein mixtures, (b) high mass range detection (>200 kDa), (c) high sensitivity (fmol range), (d) ability to sequence peptides using post-source decay spectra and "ladder sequencing", (e) high-throughput and automated analyses for identification of unknown proteins.